The main aim of this research is to further our studies on porphyrin metabolism which we are developing under Grant GM-11973. During our present work we developed methods for the synthesis of uroporphyrins and protoporphyrins. We established that coproporphyrinogen IV is enzymically decarboxylated to a protoporphyrin for which we propose the structure of protoporphyrin IV. This protoporphyrin IV is enzymically transformed into a hemin IV. All those enzymatic reactions take place in very good yields. A synthetic program was designed to obtain all four protoporphyrin isomers (protoporphyrin III, protoporphyrin IV, protoporphyrin II, and protoporphyrin I). Efficient and simple reactions are being used to obtain all isomers in good yields. This involves synthesis of a few crucial pyrroles to be used in all synthesis, use of efficient compling reactions to afford dipyrrylmethanes and alpha, alpha'-free dipyrrylmethanes to obtain porphyrins. The synthetic "iso"-hemins obtained from the isomeric protoporphyrins will be used to study their effect in promoting "iso"-hemoglobin synthesis in iron-deprived rabbit reticulocytes. They will also be bound to globin by using a chemical recombination. The obtained "iso"-hemoglobins will be examined in their biological oxygen-binding activity and in the chemical properties. The synthetic "iso"-hemins will also be examined as substrates of hemin oxygenase to obtain information about their possible "in vivo" stability in pharmacological trials.